Now, That's What I Call High-Yield: Pharmacology

Studying pharmacology may throw you back to the days of studying general chemistry…molar concentrations, reaction rates, solubility, oh my! Luckily for you, that means you have seen these topics before and can apply them to clinical questions. Step 1 pharmacology is easier than those general chemistry final exams—you can use context clues, process of elimination, and quick math hacks to pick up easy points throughout the test. No need to ph-ear pharmacology!

As with all subjects, you should take a systematic approach to study pharmacology. Start with a brief overview of some general chemistry and biology concepts: solubility, reaction rates, and enzyme mechanics. Next, move on to the autonomic nervous system, where we find the ultra-high yield G-protein (e.g. alpha, beta) receptors. Finally, review general toxidromes and big picture side effects of drug classes. Voila! You will have a solid pharmacology foundation.

Once you feel confident with the basic concepts, review the high-yield terms and equations to build on your foundation. Remember, taking the time to learn and practice these concepts will help throughout the whole test—and clinical rotations.

Here are some general concepts to familiarize yourself with before diving into the list of high-yield topics to review (with their corresponding chapters and pages from First Aid).

High-Yield Pharmacology Topics for USMLE Step 1

Topic (First-Aid Chapter)

Inhibitors (6.5)

Understand the difference between competitive and noncompetitive inhibitors. The nitty-gritty details of the Michaelis-Menten kinetics and Lineweaver-Burk plots were important for the MCAT, but less relevant for STEP1. Understanding the variables and what they generally mean might help you with a question or two on the test.

Toxicity treatment (7)

You will definitely see a passage describing a drug overdose/intoxication on the exam. Which one? Who’s to say…

Among the most important with their respective antidotes are Acetaminophen (N-actetylcysteine), benzodiazepines (flumazenil), carbon monoxide (100% [+/- hyperbaric] oxygen), heparin (protamine), methanol (fomepizole), opioids (naloxone), and warfarin (vitamin K and fresh frozen plasma). Familiarize yourself with the symptoms and potential treatment options to counteract the overdose. For example, if someone overdoses on an anticoagulant, reverse it! Someone has increased lactic acid to do an acetaminophen overdose, add base to buffer the pH.

CNS/PNS Anatomy (7.5)

Understanding the anatomy of the nervous system will help you reason through when, where, and how different drugs function. You will apply neural anatomy to neurology questions too. Key takeaways here are as follows:

Parasympathetic preganglionic AND postganglionic neurons use acetylcholine (ACh) as a messenger
Sympathetic preganglionic neurons use ACh, but sympathetic postganglionic neurons use epinephrine and norepinephrine (with the exception of sweat glands, which use ACh for both)
Voluntary muscles use ACh as a messenger at a nicotinic ACh receptor
Muscarinic ACh receptors are found in the heart, brain, and smooth muscle (very clinically significant for bronchial dilation and constriction)

Atropine (and antimuscarinic toxidrome) (7.5)

Atropine is a key drug, as it blocks muscarinic (parasympathetic drive) on both sides of the blood-brain barrier so that it can lead to a bit of mad[as a hatter]ness. If you remember the DUMBELSS acronym of your cholinergic-crisis farmer in an organophosphate-laden crop maze, atropine will cause the opposite, and cure him at the same time. Classic tried-and-true mnemonic to remember the toxidrome: Mad as a hatter, red as a beet, hot as a hare, dry as a bone, blind as a bat.

Beta blockers (8.5)

Super-clinically relevant drug class. These drugs are used for hypertension, heart failure, angina, post-MI, supraventricular tachycardia, essential tremor, and even more. Be familiar with their function (block the stimulatory Gs protein!), adverse effects and toxicity (bradycardia, sedation, sexual dysfunction), and antidote (atropine and/or glucagon).

Sympathomimetics (9)

High, high-yield. Among the most important here is Epinephrine. The prefix epi-, greek for above, means epi hits all types of 𝝰 & 𝛃 receptors, with 𝛃 being affected more than 𝝰. Norepinephrine hits all the same receptors except (nor) 𝛃2. Isoproterenol (or iso𝛃roterenol) is isolated to 𝛃 receptors. Your “pure” 𝛃2 agonists, like albuterol, are most clinically relevant for bronchodilation. There is always a bit of overlap with 𝛃1 receptors, so administration can cause tachycardia. Do𝛃utamine whips the tired heart, and is used for acute decompensated heart failure. Rounding them out is dopamine, another pressor for shock.

G-protein linked second messengers (9.5)

Easily one of the most important parts of the chapter. Knowing which G-protein type (Gi, Gq or Gs) is associated with each receptor is a must. Even more important than that, knowing where different receptors are found in the body and their function will pay dividends both on test day and throughout your medical career. The most clinically relevant receptors are 𝝰1, 𝛃1, 𝛃2, M1, M2, H1, H2, and V2. A further description of these receptors (and the drugs and endogenous chemicals that agonize & antagonize them) will warrant its own post entirely.

Reference Guide

Topic (First Aid pages)

1. Autonomic Pharmacology (pp. ~230–239)

Receptor physiology (α₁, α₂, β₁, β₂, M₁–M₃, D₁, D₂, H₁, V₁, V₂)
Sympathomimetics (epi, NE, dopamine, isoproterenol, phenylephrine, albuterol)
Parasympathomimetics (bethanechol, pilocarpine)
Anticholinergics (atropine, ipratropium, scopolamine)
Adrenergic blockers (prazosin, propranolol, metoprolol)
Cholinesterase inhibitors (neostigmine, physostigmine, organophosphates)

2. Cardiovascular Pharmacology (pp. ~296–312)

Antihypertensives (ACE inhibitors, ARBs, β-blockers, diuretics, CCBs)
Heart failure drugs (digoxin, ARNI, SGLT2 inhibitors)
Antianginals (nitrates, ranolazine)
Antiarrhythmics (Class I–IV, adenosine, magnesium)
Lipid-lowering drugs (statins, fibrates, niacin, ezetimibe, PCSK9 inhibitors)

Also see: Cardiovascular – Physiology & Pathology (for integration)

3. Respiratory & Renal Pharmacology (pp. ~316–322) and (pp. ~324–329)

Asthma/COPD drugs (β₂-agonists, corticosteroids, leukotriene modifiers, theophylline)
Diuretics (loop, thiazide, K⁺-sparing, osmotic)
RAAS inhibitors (ACEi, ARB, aliskiren)
Carbonic anhydrase inhibitors (acetazolamide)

4. Antimicrobial Pharmacology (pp. ~144–182)

Mechanisms of action & resistance
β-lactams, vancomycin, aminoglycosides, tetracyclines, macrolides, clindamycin, linezolid
Fluoroquinolones, metronidazole, TMP-SMX
Antifungals (azoles, amphotericin B, echinocandins)
Antivirals (NRTIs, NNRTIs, protease inhibitors, acyclovir, oseltamivir)
Anti-TB (RIPE regimen)

5. Central Nervous System Pharmacology (pp. ~270–295)

Sedatives & hypnotics (BZDs, barbiturates, Z-drugs)
Antidepressants (SSRIs, SNRIs, TCAs, MAOIs, atypicals)
Antipsychotics (typical vs atypical, EPS, metabolic effects)
Antiepileptics (phenytoin, valproate, carbamazepine, lamotrigine, etc.)
Parkinson’s drugs (L-DOPA, COMT/MAO inhibitors, dopamine agonists)
Opioids and antagonists
Anesthetics (inhaled, IV, local)

7. Endocrine & Metabolic Pharmacology (pp. ~332–347)

Insulin & oral hypoglycemics (metformin, SGLT2 inhibitors, GLP-1 agonists)
Thyroid drugs (levothyroxine, methimazole, PTU)
Adrenal drugs (glucocorticoids, mineralocorticoids, inhibitors like ketoconazole)
Reproductive drugs (SERMs, PDE5 inhibitors, OCPs, antiandrogens)
Bone metabolism (bisphosphonates, denosumab, teriparatide)

8. Pharmacokinetics, Dynamics, & Adverse Effects (pp. ~220–229)

Absorption, distribution, metabolism, excretion
Volume of distribution, clearance, half-life
Potency vs efficacy, agonist/antagonist interactions
CYP450 inducers/inhibitors
Teratogens and pregnancy categories
Notorious side effects (gray baby, torsades, agranulocytosis, Stevens-Johnson, etc.)